VITEK 2 AST-Streptococcus Cefuroxime (<=0.125 - >=8 µg/mL)

{0} FDA U.S. FOOD &amp; DRUG ADMINISTRATION # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY ## I Background Information: A 510(k) Number K260281 B Applicant bioMérieux, Inc. C Proprietary and Established Names VITEK 2 AST-Streptococcus Cefuroxime (≤0.125 - ≥8 μg/mL) D Regulatory Information | Product Code(s) | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | LON | Class II | 21 CFR 866.1645 - Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System | MI - Microbiology | | LTT | Class II | 21 CFR 866.1640 - Antimicrobial susceptibility test powder | MI - Microbiology | | LTW | Class II | 21 CFR 866.1640 - Antimicrobial susceptibility test powder | MI - Microbiology | ## II Submission/Device Overview: ### A Purpose for Submission: To obtain a substantial equivalence determination for the VITEK 2 AST-Streptococcus Cefuroxime (≤0.125 - ≥8 μg/mL) assay for testing of Streptococcus pneumoniae on the VITEK 2, VITEK 2 Compact, and VITEK COMPACT PRO Antimicrobial Susceptibility Test (AST) Systems. Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov {1} B Measurand: Cefuroxime ≤0.125 - ≥8 μg/mL C Type of Test: Automated quantitative or qualitative antimicrobial susceptibility test III Intended Use/Indications for Use: A Intended Use(s): See Indications for Use below. B Indication(s) for Use: VITEK 2 AST-Streptococcus Cefuroxime (≤0.125 - ≥8) is designed for antimicrobial susceptibility testing of Streptococcus species and is intended for use with the VITEK 2 Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK 2 AST-Streptococcus Cefuroxime (≤0.125 - ≥8) is a quantitative test. Testing is indicated for Streptococcus pneumoniae as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC). VITEK 2 AST-Streptococcus Cefuroxime (≤0.125 - ≥8) has demonstrated acceptable performance with the following organism: Streptococcus pneumoniae The VITEK 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Streptococcus pneumoniae, beta-hemolytic Streptococcus and Viridans Streptococcus to antimicrobial agents when used as instructed. C Special Conditions for Use Statement(s): Rx – For Prescription Use Only Due to the occurrence of very major errors, perform an alternative method of testing prior to reporting of results for the following antibiotic/organism combination: Cefuroxime (cxm01n): S. pneumoniae when the VITEK2 MIC is 0.5 μg/mL (based on parenteral breakpoints) D Special Instrument Requirements: VITEK 2 Systems (i.e., VITEK 2, VITEK 2 Compact, and VITEK COMPACT PRO), Software version 10.1 or newer K260281 - Page 2 of 12 {2} K260281 - Page 3 of 12 # IV Device/System Characteristics: ## A Device Description: The VITEK 2 AST card is a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK 2 AST card contains 64 wells. A control well which contains only nutrient medium is resident on all cards. The remaining wells contain premeasured portions of antimicrobials combined with the nutrient media. The isolate to be tested is diluted to a standardized concentration with 0.45% to 0.50% saline before being used to rehydrate the antimicrobial medium within the card. VITEK 2 AST cards are intended to be used with VITEK 2 System instruments (VITEK 2, VITEK 2 Compact, and VITEK COMPACT PRO). The VITEK 2 System is a fully automated instrument that integrates sample preparation, incubation, and optical measurement for microbial identification and antimicrobial susceptibility testing (AST). The VITEK 2 System will automatically (or allow operator to manually) dilute the organism suspension to prepare an inoculum for susceptibility cards. Then, the VITEK 2 will fill, seal and place the card into the incubator/reader. The VITEK 2 Compact and VITEK COMPACT PRO have a manual filling, sealing, and loading operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time. The analysis program determines when a well demonstrates growth based on attenuation of light measured by an optical scanner. The data are used to determine the MIC values for the antimicrobial agent. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card. VITEK 2 AST-ST Cefuroxime has the following concentrations in the card: 0.25, 0.5, 1 and 2 µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 AST-ST Cefuroxime test is ≤0.125 - ≥8 µg/mL. ## B Principle of Operation: The VITEK 2 AST cards use an abbreviated doubling dilution series of antimicrobial to establish the MIC. Each VITEK 2 AST card contains 64 wells—one “growth” control well contains nutrient medium only, and the remaining wells contain premeasured antimicrobials in nutrient media. The VITEK 2 System instruments (VITEK 2, VITEK 2 Compact, and VITEK COMPACT PRO) utilize automated growth-based detection using attenuation of light measured by an optical scanner. The optics in the VITEK 2 Systems use visible light to directly measure organism growth within each of the 64 micro-wells. Transmittance optics is based on an initial light reading of a well before significant growth has begun. Every 15 minutes throughout the incubation cycle (defined period of time based on the VITEK 2 AST card), light transmittance readings of each well determine organism growth by the amount of light that is prevented from passing through the well. At the completion of the incubation period, the MIC values and their associated interpretive category results for each antimicrobial on the test card are displayed in an automatically generated report. {3} V Substantial Equivalence Information: A Predicate Device Name(s): VITEK 2 AST-Streptococcus Penicillin (≤0.06 - ≥8 μg/mL) B Predicate 510(k) Number(s): K232201 C Comparison with Predicate(s): | Device & Predicate Device(s): | Device: K260281 | Predicate: K232201 | | --- | --- | --- | | Device Trade Name | VITEK 2 AST-Streptococcus Cefuroxime (≤0.125 - ≥8 μg/mL) | VITEK 2 AST-Streptococcus Penicillin (≤0.06 - ≥8 μg/mL) | | General Device Characteristic Similarities | | | | Indications For Use | VITEK 2 AST-Streptococcus Cefuroxime (≤0.125 - ≥8) is designed for antimicrobial susceptibility testing of Streptococcus species and is intended for use with the VITEK 2 Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK 2 AST-Streptococcus Cefuroxime (≤0.125 - ≥8) is a quantitative test. Testing is indicated for Streptococcus pneumoniae as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC). VITEK 2 AST-Streptococcus Cefuroxime (≤0.125 - ≥8) has demonstrated acceptable performance with the following organism: Streptococcus pneumoniae The VITEK 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Streptococcus pneumoniae, beta-hemolytic Streptococcus | VITEK 2 Streptococcus Penicillin is designed for antimicrobial susceptibility testing of Streptococcus species and is intended for use with the VITEK 2 and VITEK 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK 2 Streptococcus Penicillin is a quantitative test. Penicillin has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active both in vitro and in clinical infections: Beta hemolytic streptococci groups C and G Streptococcus pyogenes Streptococcus agalactiae Streptococcus viridans group Streptococcus pneumoniae The VITEK 2 Streptococcus Susceptibility Card is intended for use with the VITEK 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Streptococcus pneumoniae, beta-hemolytic Streptococcus, and Viridans Streptococcus to antimicrobial agents when used as instructed. | K260281 - Page 4 of 12 {4} | | and Viridans Streptococcus to antimicrobial agents when used as instructed. | | | --- | --- | --- | | Test Methodology | Automated quantitative antimicrobial susceptibility test for use with the VITEK 2 Systems to determine the in vitro susceptibility of microorganisms | Same | | Inoculum | Saline suspension of organism | Same | | Test Card | VITEK 2 Streptococcus Susceptibility Test Card | Same | | General Device Characteristic Differences | | | | Antimicrobial Agent | Cefuroxime | Penicillin | | Antimicrobial Concentrations | 0.25, 0.5, 1, 2 μg/mL | 0.06, 0.12, 0.5, 2 μg/mL | | Instrument | VITEK 2, VITEK 2 Compact, and VITEK COMPACT PRO Systems | VITEK 2 and VITEK 2 Compact Systems | | Analysis Algorithm | Growth Pattern Analysis | Discriminant Analysis | | Base Broth | Modified ST1 | ST4 | | Tested Species | Streptococcus pneumoniae | Beta hemolytic Streptococci groups C and G Streptococcus pyogenes Streptococcus agalactiae Streptococcus viridans group Streptococcus pneumoniae | ## Predetermined Change Control Plan (PCCP): To support the implementation of changes to FDA-recognized susceptibility test interpretive criteria (i.e., breakpoints), this submission included a predetermined change control plan (PCCP) with a breakpoint change protocol that was reviewed and accepted by FDA in submission K250274 cleared on April 30, 2025. This protocol addresses future revisions to device labeling in response to breakpoint changes that are recognized on the FDA STIC webpage (https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm410971.htm). The protocol outlined the specific procedures and acceptance criteria that bioMérieux intends to use to evaluate the VITEK 2 AST-Streptococcus Cefuroxime when revised breakpoints for cefuroxime are published on the FDA STIC webpage. The breakpoint change protocol included with the submission indicated that if specific criteria are met, bioMérieux will update the VITEK 2 AST-Streptococcus Cefuroxime label to include (1) the new breakpoints, (2) an updated performance section after re-evaluation of data in this premarket notification with the new breakpoints, and (3) any new limitations as determined by their evaluation. ## VI Standards/Guidance Documents Referenced: Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. K260281 - Page 5 of 12 {5} CLSI M07 12th Edition, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically (May 2024) CLSI M100 35th ed. Performance Standards for Antimicrobial Susceptibility Testing (January 2025) ## VII Performance Characteristics (if/when applicable): ## A Analytical Performance: 1. Precision/Reproducibility: Reproducibility testing for the VITEK 2 AST-Streptococcus Cefuroxime was conducted at three external sites using a panel of ten S. pneumoniae isolates consistent with the indications for use. Each isolate was tested in triplicate, using separate inoculum for each and tested over three days for a total of 270 data points. The inocula were prepared using both the autodilution and manual dilution methods for testing with the VITEK 2 and the manual dilution method for testing with the VITEK 2 Compact. The COMPACT PRO did not obtain premarket clearance until after the closure of the external study sites; therefore, reproducibility for the COMPACT PRO was assessed with separate inocula prepared from ten isolates and tested at one internal site with three instruments and three operators for a total of 270 data points. Additionally, due to the similarities between the two Compact systems, the VITEK 2 Compact reproducibility performance was leveraged to support the VITEK COMPACT PRO. Taken together, this was considered acceptable. For analysis of the data, the mode of MIC values was determined for each isolate and the reproducibility was calculated based on the number of MIC values that fell within ± one doubling dilution of the mode MIC value. Both best-case and worst-case scenarios were analyzed per FDA Class II Special Controls Guidance. The majority of data points were on-scale and within ± one doubling dilution agreement as compared to the mode MIC. The reproducibility performance is shown in Table 1. For the VITEK COMPACT PRO, the worst-case scenario reproducibility was 80% due to two isolates with off-scale modes, which were previously on-scale for cefuroxime when tested two years prior with the VITEK 2 and VITEK 2 Compact. Additional testing was performed with the manual dilution method with the VITEK 2 and VITEK COMPACT PRO. Results were off-scale for both instruments, indicating that results were likely due to isolate variability and not reproducibility issues with the instruments. Taken together, the results are acceptable. Table 1. Reproducibility Performance of VITEK 2 AST-Streptococcus Cefuroxime | | VITEK 2 | | VITEK 2 Compact | VITEK COMPACT PRO | | --- | --- | --- | --- | --- | | | Auto-Dilution | Manual Dilution | Manual Dilution | Manual Dilution | | Best-Case | 98.1% | 98.5% | 98.1% | 94.1% | | Worst-Case | 94.4% | 95.9% | 100% | 80.0% | K260281 - Page 6 of 12 {6} 2. Linearity: Not applicable. 3. Analytical Specificity/Interference: Not applicable. 4. Detection Limit and Assay Reportable Range: Not applicable. 5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods): # Quality Control (QC) Testing: The CLSI recommended QC strain Streptococcus pneumoniae ATCC 49619 was tested as sufficient number of times (i.e., at least 20/site) at each testing site using the VITEK 2 AST-Streptococcus Cefuroxime and Broth Microdilution (BMD) reference method. Both the automatic dilution and manual dilution methods were used for the VITEK 2 and the manual dilution method was used for the VITEK 2 Compact and VITEK COMPACT PRO. The results are summarized in Table 2 below. Both the auto-dilution and manual dilution methods for VITEK 2 and the manual dilution methods for VITEK 2 Compact and VITEK COMPACT PRO QC results were within the expected range $&gt;95\%$ of the time. Table 2. Quality Control Results for VITEK 2 AST-Streptococcus Cefuroxime | Organism | VITEK 2 Result Range (μg/mL) | BMD Result Range (μg/mL) | VITEK 2 Auto Dilution | BMD | VITEK 2 Manual Dilution | BMD | VITEK 2 Compact Manual Dilution | BMD | VITEK COMPACT PRO Manual Dilution | BMD | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Streptococcus pneumoniae ATCC 49619Expected Results:0.25-1 μg/mL | | ≤0.0625 | | 1 | | | | | | | | | 0.125 | 0.125 | 2 | 4 | | 2 | | 2 | | | | | 0.25 | 0.25 | 34 | 179 | 7 | 88 | 8 | 88 | 1 | 22 | | | 0.5 | 0.5 | 153 | 5 | 83 | | 82 | | 21 | | | | 1 | 1 | | | | | | | | | | | 2 | 2 | | | | | | | | | | | 4 | 4 | | | | | | | | | | | 8 | 8 | | | | | | | | | | | | 16 | | | | | | | | | | | | ≥32 | | | | | | | | | Two ancillary QC organisms, Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922, were tested throughout comparative testing by the BMD reference method only to ensure further quality control of the BMD panels. QC results for the BMD reference method were within the expected result range $100\%$ (125/125) of the time for S. aureus ATCC 29213 and $99.2\%$ (123/124) of the time for E. coli ATCC 25922. K260281 - Page 7 of 12 {7} K260281 - Page 8 of 12 ## Inoculum Density Control: The DensiCHEK Plus was used to standardize the inoculum to a 0.5 McFarland standard. The instrument was standardized daily with all results recorded at each site. Calibration values were within the expected range. ## Purity Check: A purity check of all organisms was performed on the dilution tube used to prepare the VITEK 2 card inoculum. Only those cultures that were pure were evaluated in the study. ## Device Failure: During the performance of the comparative study, there were zero (0) device failures with the VITEK 2 System instruments. ## Growth Failure Rate: A total of 353 clinical and challenge isolates were tested by VITEK 2 AST-ST Cefuroxime. No growth failures were recorded, and all 353 isolates had VITEK 2 AST results available. ## 6. Assay Cut-Off: Not applicable. ## B Comparison Studies: ### 1. Method Comparison with Predicate Device: Testing of cefuroxime was performed at three external sites and one internal site. Results obtained with VITEK 2 AST-Streptococcus Cefuroxime were compared to results obtained with the CLSI broth microdilution reference panel. The MIC result range for the VITEK 2 AST-Streptococcus Cefuroxime is ≤0.125 - ≥8 μg/mL for *S. pneumoniae*. The testing conditions for the reference method consisted of the following: - Medium: 2.5% to 5% LHB-supplemented CAMHB - Inoculum: Direct colony suspension - Incubation: 35°C; 20-24 hours The VITEK 2 cards were inoculated with test organisms using the auto-dilution method (VITEK 2) and using the manual dilution method (VITEK 2, VITEK 2 Compact, VITEK COMPACT PRO). All test inocula used for the VITEK 2 AST cards and the reference method were standardized using the DensiCHEK instruments. A total of 303 *S. pneumoniae* clinical isolates were evaluated using auto-dilution and VITEK 2. Of these isolates, 38.3% were contemporary isolates (tested within six months of isolation) and 61.7% were stock isolates (no specific time from isolation). A total of 50 *S. pneumoniae* challenge isolates were evaluated at one external site (VITEK 2 and VITEK 2 Compact) or one internal site (VITEK COMPACT PRO). ## Clinical and Challenge Data – VITEK 2 Auto-Dilution The results obtained using the auto-dilution method of the VITEK 2 from the 353 total isolates (303 clinical isolates and 50 challenge isolates) are summarized in Table 3. {8} Table 3. Performance of All Clinical and Challenge Isolates for Cefuroxime: VITEK 2 Auto-Dilution | | Total | #EA | %EA | Eval EA Total | Eval EA # | Eval EA % | #CA | %CA | #R | #S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Streptococcus pneumoniae Parenteral Breakpoints ≤0.5 (S), 1 (I), ≥2 (R) | | | | | | | | | | | | | | | Clinical | 303 | 287 | 94.7 | 52 | 36 | 69.2 | 296 | 97.7 | 62 | 239 | 2 | 0 | 5 | | Challenge | 50 | 50 | 100 | 22 | 22 | 100 | 49 | 98 | 41 | 8 | 1 | 0 | 0 | | Combined | 353 | 337 | 95.5 | 74 | 58 | 78.4 | 345 | 97.7 | 103 | 247 | 3 | 0 | 5 | | Streptococcus pneumoniae Oral Breakpoints ≤1 (S), 2 (I), ≥4 (R) | | | | | | | | | | | | | | | Clinical | 303 | 287 | 94.7 | 52 | 36 | 69.2 | 290 | 95.7 | 56 | 241 | 12 | 0 | 1 | | Challenge | 50 | 50 | 100 | 22 | 22 | 100 | 47 | 94 | 39 | 9 | 3 | 0 | 0 | | Combined | 353 | 337 | 95.5 | 74 | 58 | 78.4 | 337 | 95.5 | 95 | 250 | 15 | 0 | 1 | EA - Essential Agreement CA - Category Agreement Eval - Evaluable isolates R - Resistant min - Minor Discrepancies maj - Major Discrepancies vmj - Very Major Discrepancies S - Susceptible Essential agreement (EA) occurs when the result of the reference method and that of the VITEK 2 AST card are within plus or minus one serial two-fold dilution of the antibiotic. Evaluable results are those that are on-scale for both the reference method and VITEK 2 AST card or results in which an off-scale result is at least two doubling dilutions from the on-scale result. Category agreement occurs when the interpretation of the result of the reference method agrees exactly with the interpretation of the VITEK 2 AST card. For testing S. pneumoniae with the auto-dilution method of the VITEK 2, the EA was acceptable at $95.5\%$ (Table 3). Using the parenteral breakpoints for S. pneumoniae with the auto-dilution method of the VITEK 2, the CA was acceptable at $97.7\%$ and there were three minor errors, zero major errors, and five very major errors $(4.9\%)$ . The very major error rate was not acceptable. To address the unacceptable very major error rate, the following limitation was included in the device labeling: Due to the occurrence of very major errors, perform an alternative method of testing prior to reporting of results for the following antibiotic/organism combination: Cefuroxime (cxm01n): S. pneumoniae when the VITEK2 MIC is $0.5\mu \mathrm{g} / \mathrm{mL}$ (based on parenteral breakpoints) Using the oral breakpoints for S. pneumoniae with the auto-dilution method of the VITEK 2, the CA was acceptable at $95.5\%$ and there were 15 minor errors, zero major errors, and one very major error $(1.1\%)$ . # Challenge Data -VITEK 2, VITEK 2 Compact, and VITEK COMPACT PRO Manual Dilution The 50 challenge isolates were also evaluated at one external site with the manual dilution option of the VITEK 2 and VITEK 2 Compact Systems, and one internal site with the VITEK COMPACT PRO (summarized in Table 4). K260281 - Page 9 of 12 {9} Table 4. Performance of Challenge Isolates for Cefuroxime: VITEK 2, VITEK 2 Compact and VITEK COMPACT PRO Manual Dilution | VITEK 2 Systems | Total | #EA | %EA | Eval Total | Eval EA # | Eval EA % | #CA | %CA | #R | #S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Streptococcus pneumoniae Parenteral Breakpoints ≤0.5 (S), 1 (I), ≥2 (R) | | | | | | | | | | | | | | | VITEK 2 | 50 | 50 | 100 | 22 | 22 | 100 | 49 | 98 | 41 | 8 | 1 | 0 | 0 | | VITEK 2 Compact | 50 | 50 | 100 | 22 | 22 | 100 | 49 | 98 | 41 | 8 | 1 | 0 | 0 | | VITEK COMPACT PRO | 50 | 50 | 100 | 13 | 13 | 100 | 49 | 98 | 41 | 8 | 1 | 0 | 0 | | Streptococcus pneumoniae Oral Breakpoints ≤1 (S), 2 (I), ≥4 (R) | | | | | | | | | | | | | | | VITEK 2 | 50 | 50 | 100 | 22 | 22 | 100 | 47 | 94 | 39 | 9 | 3 | 0 | 0 | | VITEK 2 Compact | 50 | 50 | 100 | 22 | 22 | 100 | 47 | 94 | 39 | 9 | 3 | 0 | 0 | | VITEK COMPACT PRO | 50 | 50 | 100 | 13 | 13 | 100 | 47 | 94 | 39 | 9 | 3 | 0 | 0 | EA - Essential Agreement CA - Category Agreement Eval - Evaluable isolates R - Resistant min - Minor Discrepancies maj - Major Discrepancies vmj - Very Major Discrepancies S - Susceptible Essential agreement (EA) occurs when the result of the reference method and that of the VITEK 2 AST card are within plus or minus one serial two-fold dilution of the antibiotic. Evaluable results are those that are on-scale for both the reference method and VITEK 2 AST card or results in which an off-scale result is at least two doubling dilutions from the on-scale result. Category agreement occurs when the interpretation of the result of the reference method agrees exactly with the interpretation of the VITEK 2 AST card. For testing S. pneumoniae with the manual dilution method of the VITEK 2, the EA was acceptable at 100%. Similarly, the EA was acceptable at 100% with the manual dilution method of both the VITEK 2 Compact and the VITEK COMPACT PRO. Using parenteral breakpoints, the overall performance of the VITEK 2 AST-Streptococcus Cefuroxime when testing S. pneumoniae with the manual dilution method was acceptable with a CA of 98.0%, and one minor error and no major or very major errors. Similarly, the CA was acceptable at 98.0% and one minor error and no major or very major errors with the manual dilution method of both the VITEK 2 Compact and the VITEK COMPACT PRO. Using oral breakpoints, the overall performance of the VITEK 2 AST-Streptococcus Cefuroxime when testing S. pneumoniae with the manual dilution method was acceptable with a CA of 94.0%, and three minor errors and no major or very major errors. Similarly, the CA was acceptable at 94.0% and three minor errors and no major or very major errors with the manual dilution of both the VITEK 2 Compact and the VITEK COMPACT PRO. ## MIC Trending A trending analysis was conducted using the combined data (clinical and/or challenge) obtained for Streptococcus pneumoniae. This trending calculation takes into account MIC values that are determined to be one or more doubling dilutions lower or higher than the reference method irrespective of whether the device MIC values are on-scale or not. K260281 - Page 10 of 12 {10} Species for which the difference between the percentage of isolates with higher vs. lower readings was $\geq 30\%$ and for which the confidence interval was determined to be statistically significant were considered to show evidence of trending. Trending that shows higher or lower MIC values compared to the reference is addressed in the labeling. Table 5. Trending for *Streptococcus pneumoniae* with Cefuroxime and the VITEK 2 Systems | Organism | Inoculation/ Read Method | Total Evaluable for Trending | ≥ 1 Dilution lower No. (%) | Exact No. (%) | ≥ 1 Dilution Higher No. (%) | Percent Difference (CI) | Trending Noted | | --- | --- | --- | --- | --- | --- | --- | --- | | *Streptococcus pneumoniae* | Auto/ VITEK 2 | 110 | 68 (61.8) | 32 | 10, (9.1) | -53% (-62%, -41%) | Yes | | | Manual/ VITEK 2 | 25 | 8 (32.0) | 13 | 4, (16.0) | -16% (-38%, 8%) | No | | | Manual/ VITEK 2 Compact | 24 | 7 (29.2) | 14 | 3, (12.5) | -17% (-38%, 7%) | No | | | Manual/ VITEK COMPACT PRO | 21 | 4 (19.1) | 8 | 9, (42.9) | 24% (-4%, 47%) | No | A trend toward lower MIC values was observed for *S. pneumoniae* when compared to the CLSI broth microdilution reference method, as summarized in Table 5. The following statement is included as a footnote to the performance table in the device labeling to address the observed trending: &gt; VITEK 2 AST–Streptococcus Cefuroxime MIC values tended to be in exact agreement or at least one doubling dilution lower when testing *Streptococcus pneumoniae* by VITEK 2 auto-dilution method compared to the CLSI reference broth microdilution method. ## Testing/Reporting MICs for Species Not Listed in the Indications for Use For this review, the interpretive criteria are applied to the organisms/organism groups according to the FDA STIC website. As required under 511A(b)(2)(C)(ii)(I) of the Federal Food, Drug and Cosmetic Act, the following statement was added to the package insert to address testing and reporting of species not listed in the Indications for Use: &gt; Per the FDA-Recognized Susceptibility Test Interpretive Criteria website, the safety and efficacy of antimicrobial drugs, for which antimicrobial susceptibility is tested by this AST device, may or may not have been established in adequate and well-controlled clinical trials for treating clinical infections due to microorganisms outside of those found in the indications and usage in the drug label. The clinical significance of susceptibility information in those instances is unknown. The approved labeling for specific antimicrobial drugs provides the uses for which the antimicrobial drug is approved. K260281 - Page 11 of 12 {11} 2. Matrix Comparison: Not applicable. # C Clinical Studies: 1. Clinical Sensitivity: Not applicable. 2. Clinical Specificity: Not applicable. 3. Clinical Cut-Off: Not applicable. 4. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable): Not applicable. # D Expected Values/Reference Range: Table 6. FDA-Approved or Recognized Interpretive Criteria | Organism | Minimum Inhibitory Concentrations (μg/mL)a | | | | --- | --- | --- | --- | | | Susceptible | Intermediate | Resistant | | Streptococcus pneumoniae | Parenteral Breakpoints | | | | | ≤0.5 | 1 | ≥2 | | | Oral Breakpointsb | | | | | ≤1 | 2 | ≥4 | a According to FDA STIC Webpage, https://www.fda.gov/drugs/development-resources/fda-recognized-antimicrobial-susceptibility-test-interpretive-criteria b Interpretations for oral cefuroxime may be reported for isolates other than those from CSF # VIII Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. # IX Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. K260281 - Page 12 of 12